3. DEFINITION
Cryptococcal meningitis is an infection leading to
an inflammation of the meninges caused by
fungus mainly Cryptococcus after it spreads from
the lungs to the brain.
Unlike other types of meningitis, here the
duration of symptoms before presentation is likely
to be longer in non-AIDS patients, with a history
of more than 2 weeks in only 25% of HIV positive
patients.
4. EPIDEMIOLOGY
C. neoformans is a major cause of meningitis in people living with
HIV/AIDs, with an estimated 1 million cases occurring world wide each
year.
Most cases occur in the 20- 50 years age group.
8. PATHOPHYSIOLOGY
The initial step in fungal meningitis is the pulmonary exposure to
the fungi by the inhalation of airborne fungal spores.
Inflammation results leading to a primary pulmonary and lymph
node focus limiting the inhaled organism from further spread.
The pulmonary infection is usually self limited and maybe
asymptomatic.
With an associated impaired immune response the fungus may
disseminate e.g. in Cryptococcal infection, the fungus may remain
dormant in the lungs until the immune system weakens and can
the reactivate and disseminate to the CNS. Cryptococcus has
predilection for CNS dissemination, the presence of a receptor on
glial cells for a ligand on the organism enhances its invasion.
Once the fungi cross the BBB, they cause an inflammation of the
meninges and arachnoid space.
9. CONTD…
The inflammation promotes cytokine release mainly Tumor
Necrosis Factor(TNF), IL-1, IL-2, IL-6, IL-12, Colony-
stimulating factors and interferon gamma.
Cytokines cause the fever and promote an increase in
permeability of BBB and subsequent cerebral edema and
Increased Intracranial Pressure.
Cerebral edema leads to decreased blood flow to the brain
and hypoxia.
The glucose levels in the CSF will decrease due to a
decreased transport of glucose coupled to an increased use
of glucose by the fungi. The increase in permeability of the
BBB is the cause of the observed elevation of the protein
levels in the CSF.
10. CLINICAL FEATURES
Severe headache
Sudden high fever
Neck pain, stiffness and rigidity
Nausea and vomiting
Lethargy
Personality change
Memory loss
Photophobia
Joint pain
Seizures
Sleepiness or difficulty waking
Confusion or changes in behavior
11. WHO’S AT RISK
Age (20 TO 50 YEARS)
All HIV-infected ART naïve with CD4<200 cells/mm3.
ART experienced PLHIV returning to care after 90 days of treatment
interruption with CD4<200 cells/mm3.
All HIV-infected virologically unsuppressed patients with CD4<200 cells/mm3.
All patients with WHO stage 3 or 4 event.
All PLHIV who have a positive symptom screen on the Advanced Disease
Pathway.
12. PHYSICAL EXAMINATION
Mental status
Cranial nerve assessment (Esp. III, IV, VI, and VII)
Motor function
Meningeal irritaion signs (Stiff neck,Kernig sign)
Lethargy/Unconsciousness
Abnormal movements/Ataxia
13. INVESTIGATIONS
Definitive diagnosis requires CSF analysis with
demonstration of yeasts with Indian Ink Stain, positive
Cryptococcal antigen testing or culture of the organism.
CSF EXAMINATION
Reveals a mild mononuclear leukocytosis (50-500 cells/UL)
CSF protein is rarely greater than 500-1000 mg/dl and it
may be normal especially in HIV patients.
In HIV patients, the cell count is usually much lower, often
in single figures.
14. CONTD…
IMAGING
Brain CT scan is normal in 50% of patients, the most
common abnormal finding is hydrocephalus.
MRI is more likely to show abnormalities than CT scan.
DIAGNOSTIC TECHNIQUES:
India Ink Test:
This is usually for rapid diagnosis.
Yeast cells are easily identified through the halo effect
that occurs around them because of glucuronoxylomannan
capsule.
A concentration of yeasts less than 104 colony forming
units is unlikely to be detected.
15. CONTD…
Culture:
C. neoformans from CSF or blood grows readily on blood agar at 35 degrees.
Identification can be confirmed through the demonstration of capsule growth
on corn meal agar, development of characteristic brown mucoid colonies on
birdseed agar, and through commercially available sugar assimilation test kits.
C. neoformans grows easily in commercially available automated blood
culture systems. Culture of CSF is more sensitive in detecting Cryptococcal
infection than the India ink test, with a sensitivity of about 90%.
Cryptococcal Antigen:
Antigen testing is both sensitive and specific in identifying patients with
Cryptococcal disease.
The kits can be used on serum or CSF and the sensitivity in CSF is > 90% in
Cryptococcal Meningitis.
Serotyping:
These are immuno-typing kits to distinguish the various Cryptococcal
serotypes, however they are quite expensive.
18. REHABILITATION
In case of long term complications and disability,
rehabilitation is needed to improve quality of live and
attempt to restore functionality.
Rehabilitation programs can include:
• Physiotherapy (Physical disability).
• Speech and language therapy ( Sensory
disability/deafness).
• Special needs education ( Mental retardation/learning
difficulties).
• Provision of hearing/visual aids ( Deafness/blindness).
19. PROGNOSIS
Appropriate antifungal therapy reduces the mortality rate
for Cryptococcal meningitis in patients, but mortality
remains high.
Prognosis depends on:
1. Age.
2. Causative organism.
3. Number of organisms and virulence.
4. Duration of illness prior to effective antifungal therapy.
5. Presence of disorders that may compromise host response
to infection.
20. PREVENTION
The best way to prevent cryptococcosis is to not
inhale the fungus. This is difficult to do if you live in
areas where the fungus resides.
Primary prophylaxis against Cryptococcal disease by
using Fluconazole.
Community awareness especially on risk factors.
Wash hands, proper hygiene and good sanitation.
Prompt and proper treatment for infections especially
ENT and respiratory tract.
